Inspired by the award-winning documentary, this medical drama is set in the busiest and most notorious ER in the nation where the extraordinary staff confront a challenged system in order to protect their ideals and the patients who need them the most.

The new residents are introduced to the ER. A new doctor from the army who knows many advanced procedures is flown to a shark attack on the beach with Mike Leighton and Leighton falls 20 feet from the helicopter. Dr. Guthrie Jr. is promoted to the director of the ER in addition to the OR.

Willis must help a promising soccer player make a life-altering decision after he's seriously injured, and another patient's hesitation to share that she's transgender makes it difficult for the doctors to diagnose her severe abdominal pain.

Willis defies Campbell’s orders when he helps Mario and Heather perform a radical procedure on a maintenance worker stuck under a boiler that exploded. Also, Angus’ father, Dr. Desmond Leighton, tries to seize Power of Attorney over Mike, who is still in a coma, even though Mike granted that right to his brother, Angus.

Malaya must inform a college student who regains consciousness at Angels Memorial that she's the victim of a rape. Meanwhile, Willis and Campbell butt heads over a terminally ill woman who wants to end her life on her own terms; and a comedian is treated after he collapses on stage during a performance.

Willis, Leanne and Jesse risk their lives to operate on an injured officer who has an explosive bullet lodged in her leg. Meanwhile, Mario, Noah and Guthrie treat a magician who comes to the hospital with breathing difficulties.

A 13-year-old girl arrives at Angels Memorial following a seizure caused by spina bifida and the doctors are shocked to learn she is Campbell's daughter. Meanwhile, a workaholic deaf patient and her translator are treated after their car rolls into the Los Angeles River.

A code black at Angels Memorial takes a turn for the worse when a city- wide blackout leaves the hospital without power or back-up generators. As Campbell and Leanne divert high-risk patients to a nearby care center, Elliot and Heather are trapped in an elevator with a woman in labor, and Willis and Dr. Nolan try to help a 92-year-old woman who thinks it’s 1942.

The ER is quarantined when a viral outbreak jeopardizes the lives of the doctors and patients at Angels Memorial. Also, Ariel, the young girl Leanne bonded with a year ago when she lost her father, returns to Angels.

The doctors work with the Center for Disease Control and Prevention to find an antidote to the deadly viral outbreak at Angels Memorial. Also, Leanne makes a life-changing decision, and Jesse welcomes a new batch of residents.